Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons

Kidney Int. 2009 Feb;75(3):285-94. doi: 10.1038/ki.2008.499. Epub 2008 Oct 1.

Abstract

Urinary neutrophil gelatinase-associated lipocalin (Ngal or lipocalin 2) is a very early and sensitive biomarker of kidney injury. Here we determined the origin and time course of Ngal appearance in several experimental and clinically relevant renal diseases. Urinary Ngal levels were found to be markedly increased in lipoatrophic- and streptozotocin-induced mouse models of diabetic nephropathy. In the latter mice, the angiotensin receptor blocker candesartan dramatically decreased urinary Ngal excretion. The reabsorption of Ngal by the proximal tubule was severely reduced in streptozotocin-induced diabetic mice, but upregulation of its mRNA and protein in the kidney was negligible, compared to those of control mice, suggesting that increased urinary Ngal was mainly due to impaired renal reabsorption. In the mouse model of unilateral ureteral obstruction, Ngal protein synthesis was dramatically increased in the dilated thick ascending limb of Henle and N was found in the urine present in the swollen pelvis of the ligated kidney. Five patients with nephrotic syndrome or interstitial nephritis had markedly elevated urinary Ngal levels at presentation, but these decreased in response to treatment. Our study shows that the urinary Ngal level may be useful for monitoring the status and treatment of diverse renal diseases reflecting defects in glomerular filtration barrier, proximal tubule reabsorption, and distal nephrons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute-Phase Proteins / metabolism*
  • Acute-Phase Proteins / urine
  • Albumins / metabolism
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Animals
  • Benzimidazoles / therapeutic use
  • Biomarkers / urine
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / urine
  • Disease Models, Animal*
  • Humans
  • Kidney Glomerulus / metabolism*
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism*
  • Lipocalin-2
  • Lipocalins / metabolism*
  • Lipocalins / urine
  • Loop of Henle / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / urine
  • Nephrons / metabolism*
  • Nephrotic Syndrome / metabolism
  • Nephrotic Syndrome / urine
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / urine
  • RNA, Messenger / metabolism
  • Sensitivity and Specificity
  • Tetrazoles / therapeutic use
  • Time Factors
  • Ureteral Obstruction / metabolism

Substances

  • Acute-Phase Proteins
  • Albumins
  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tetrazoles
  • candesartan